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dc.contributor.authorFerrándiz, Nuria-
dc.contributor.authorCaraballo, Juan M.-
dc.contributor.authorGarcía-Gutiérrez, Lucía-
dc.contributor.authorRodríguez-Paredes, Manuel-
dc.contributor.authorLafita, M. Carmen-
dc.contributor.authorBretones, Gabriel-
dc.contributor.authorQuintanilla, Andrea-
dc.contributor.authorMuñoz-Alonso, María J.-
dc.contributor.authorBlanco, Rosa-
dc.contributor.authorReyes, José C.-
dc.contributor.authorDelgado, M. Dolores-
dc.contributor.authorLeón, Javier-
dc.date.accessioned2012-09-14T11:57:05Z-
dc.date.available2012-09-14T11:57:05Z-
dc.date.issued2012-
dc.identifier.citationPLoS ONE 7(5): e37759 (2012)es_ES
dc.identifier.issn1932-6203-
dc.identifier.urihttp://hdl.handle.net/10261/56344-
dc.descriptionThis is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.-
dc.description.abstractIt has been previously described that p21 functions not only as a CDK inhibitor but also as a transcriptional co-repressor in some systems. To investigate the roles of p21 in transcriptional control, we studied the gene expression changes in two human cell systems. Using a human leukemia cell line (K562) with inducible p21 expression and human primary keratinocytes with adenoviral-mediated p21 expression, we carried out microarray-based gene expression profiling. We found that p21 rapidly and strongly repressed the mRNA levels of a number of genes involved in cell cycle and mitosis. One of the most strongly down-regulated genes was CCNE2 (cyclin E2 gene). Mutational analysis in K562 cells showed that the N-terminal region of p21 is required for repression of gene expression of CCNE2 and other genes. Chromatin immunoprecipitation assays indicated that p21 was bound to human CCNE2 and other p21-repressed genes gene in the vicinity of the transcription start site. Moreover, p21 repressed human CCNE2 promoter-luciferase constructs in K562 cells. Bioinformatic analysis revealed that the CDE motif is present in most of the promoters of the p21-regulated genes. Altogether, the results suggest that p21 exerts a repressive effect on a relevant number of genes controlling S phase and mitosis. Thus, p21 activity as inhibitor of cell cycle progression would be mediated not only by the inhibition of CDKs but also by the transcriptional down-regulation of key genes.es_ES
dc.description.sponsorshipThis study was supported by grants SAF08-01581 and ISCIII-RETIC RD06/0020/0017 from the Spanish Ministerio de Ciencia e Innovacion (MICINN) to JL; FIS 08/0829 to MDD; BFU2008-00238 and CSD2006-00049 from MICINN, and P06-CVI-4844 from Junta de Andalucía to JCR. NF was the recipient of a postdoctoral fellowship of the University of Cantabria.es_ES
dc.language.isoenges_ES
dc.publisherPublic Library of Sciencees_ES
dc.relation.isversionofPublisher's version-
dc.rightsopenAccesses_ES
dc.titleP21 as a transcriptional co-repressor of S-phase and mitotic control geneses_ES
dc.typeartículoes_ES
dc.identifier.doi10.1371/journal.pone.0037759-
dc.description.peerreviewedPeer reviewedes_ES
dc.relation.publisherversionhttp://dx.doi.org/10.1371/journal.pone.0037759es_ES
dc.contributor.funderInstituto de Salud Carlos III-
dc.contributor.funderMinisterio de Ciencia e Innovación (España)-
dc.contributor.funderUniversidad de Cantabria-
dc.contributor.funderJunta de Andalucía-
dc.identifier.funderhttp://dx.doi.org/10.13039/501100004587es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100004837es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100006365es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100011011es_ES
dc.identifier.pmid22662213-
dc.type.coarhttp://purl.org/coar/resource_type/c_6501es_ES
item.openairetypeartículo-
item.languageiso639-1en-
item.grantfulltextopen-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.fulltextWith Fulltext-
item.cerifentitytypePublications-
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